Genetic determinants of airways' colonisation with Pseudomonas aeruginosa in cystic fibrosis

Assessing the Disease-Liability of Mutations in CFTR

“…In general, mutations in class I to III are associated with complete or near complete loss of CFTR function (,3% of wild-type CFTR function) . Mutations in these classes are primarily associated with pancreatic insufficiency, higher rates of pulmonary infection, and higher mortality (Kubesch et al 1993;Koch et al 2001;Ahmed et al 2003;McKone et al 2003;Green et al 2010). On the other hand, residual CFTR function tends to be higher (3% -10%) in class IV and V mutations.…”

Conversion of Pseudomonas aeruginosa to mucoidy in cystic fibrosis: environmental stress and regulation of bacterial virulence by alternative sigma factors

“…In the lung, the deficiency in CFTR impairs chloride and water secretion by the respiratory epithelium (39), resulting in formation of a dehydrated, thick mucus that is difficult to clear. Although the connection between these properties and microbial colonization has been mostly anecdotal, a recent study (44) suggests a correlation between the type of CF mutations, which are often classified as "mild" or "severe" alleles of CFTR, and predisposition for colonization with P.…”

“…For example, individuals carrying one AF508 allele and the other with a mutation in the NBF-encoding exons had a four-times-higher risk of P. aeruginosa acquisition compared to compound AF508 heterozygotes with a second mutation in TM or R domains (44).…”

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-Mediated Residual Chloride Secretion Does Not Protect against Early Chronic Pseudomonas aeruginosa Infection in F508del Homozygous Cystic Fibrosis Patients

“…In this study, we addressed the issue of whether the manifestation of the CF basic defect, as assessed by the absence or presence of CFTR-mediated residual Cl Ϫ secretion, is predictive for the onset of PA colonization, as CFTR has been shown to play a key role for the acquisition of PA (14,(17)(18)(19). Among patients who are homozygous for F508del, a considerable percentage show some residual Cl Ϫ secretion (9), indicating that the CFTR mutation genotype does not exclusively predict the manifestation of the CF basic defect.…”

“…It has been reported that patients homozygous for the mutation F508del show an increased adherence of PA to the airway cells (13) and are earlier chronically colonized with PA (3, 6) than patients carrying mild CFTR mutation genotypes. Moreover, pancreatic sufficiency is associated with later acquisition of PA (14,15). The mechanism by which PA adheres to the airways is only partially known.…”